This invention relates to a mechanical breakup unit (MBU) for atomizing biochemically reactive fluids, and more particularly, a MBU in a medical fluid delivery device for separately atomizing fibrinogen and thrombin contained in separate containers to form fibrin on a surface.
One of the major problems in intra-abdominal surgery is the avoidance of post-operative adhesions. It is well-known that adhesions contribute to pain, immobility, retarded wound healing, and in particular to intestinal obstruction which may even be life-threatening. In the field of gynecological surgery, post-surgical adhesions involving female reproductive organs may result in infertility.
Each surgical procedure necessarily produces various forms of trauma where the abdominal cavity or other human cavity is opened. Physiologically, the process of wound closure then starts when bleeding ceases upon formation of a hemostatic clot at the areas of blood vessel injury. The clot, at first comprising mainly platelets, is solidified by a natural fibrin network resulting from the activation of an enzyme cascade involving thrombin, factor XIII and calcium. Further steps on the way to the sealing of the wound are retraction of the hemostatic clot, invasion of various cell types including fibroblasts into the wound area and eventually the lysis of the fibrin network. Adhesions are thought to begin forming when the fibrin clot covering an injury comes into contact with an adjacent surface and the new connective tissue produced by the fibroblasts attaches the two surfaces together.
This sometimes painful condition may often require a further operative procedure for removing/lysing the adhesions, called adhesiolysis, which, like the first operation, introduces the risk of forming additional adhesions.
Accordingly, the prevention of adhesion formation is medically important. Among the different approaches for prevention of adhesion formation, one involves the use of materials as a physical or bio-mechanical barrier for the separation or isolation of traumatized tissues during the healing process. Both synthetic materials and natural materials have been used as a barrier to adhesion formation. Some permanent inert implants, like GoreTex(copyright) surgical membranes consisting of expanded polytetra-fluoroethylene (PTFE) generally require a second operative procedure to remove them, while others, such as surgical membranes of oxidized regenerated cellulose, are biodegradable but are thought to elicit an inflammatory response ultimately leading to adhesion formation (A. F. Haney and E. Doty, Fertility and Sterility, 60, 550-558, 1993).
Fibrin sealants/glues are well-known in the art for use in hemostasis, tissue sealing and wound healing, and have been commercially available outside the United States for more than a decade. Fibrin glues have not been used for anti-adhesion purposes. Further, the practice of changing the concentrations of thrombin and fibrinogen to achieve a fibrin film having a desired pore size has also not been practiced.
Fibrin glues mimic the last step of the coagulation cascade and are usually commercialized as kits comprising two main components. The first component is a solution comprising fibrinogen and factor XIII, while the second component is a thrombin calcium solution. After the mixing of components, the fibrinogen is proteolytically cleaved by thrombin and thus converted into fibrin monomers. Factor XIII is also cleaved by thrombin into its activated form (FXIIIa). FXIIIa cross links the fibrin monomers to form a three-dimensional network commonly called xe2x80x9cFibrin Gel.xe2x80x9d
Previous attempts to provide a thrombin and fibrinogen delivery device are known. For example, one such device is disclosed in U.S. Pat. No. 4,978,336 to Capozzi et al. which discloses a dual syringe system. A device made by the assignee of the ""336 patent, Hemaedics, Inc., is sold under the tradename DUOFLO. The distal end of each syringe is attached to a common manifold having a mixing chamber. Fibrinogen and thrombin solutions are mixed in the manifold 14 prior to application to a wound or other surface. The manifold has a discharge tip for delivering the mixed solution onto a surface. A shortcoming of this device is the propensity for the tip to clog with solid fibrin being formed during brief interruptions in the application processxe2x80x94such interruptions are common in medical procedures. The likelihood of this occurring increases as the thrombin concentration increases especially thrombin concentrations of greater than 20 IU/ml. The ""336 patent acknowledges the clogging problem and suggests solving the problem by replacing the clogged tip. (Col. 3, line 4-Col. 4, line 2). However, replacing clogged tips is impractical and unacceptable for minimally invasive surgeries where a cavity of an animal body is accessed through a small surgical opening.
Other techniques teach applying beads of a solution of thrombin and calcium adjacent in contact with a solution of fibrinogen and Factor XIII on a surface. In such a case, the thrombin and fibrinogen react primarily along interfacing surfaces while the remaining portions of the solutions are generally isolated from one another by the solid fibrin formed between them. Thus, there is inadequate mixing of the solutions to provide for a suitable fibrin film. Further, the unreacted fibrinogen is now available to react with thrombin supplied by the body to promote the formation of adhesions.
U.S. Pat. No. 4,631,055 discloses another thrombin and fibrinogen delivery device having two syringes mounted in a holding frame in a parallel spaced relationship. A conical portion of a distal end of each syringe is inserted into a connecting head. In one embodiment of the ""055 patent, mixing of fluids contained in each syringe occurs inside the connecting head and in another embodiment the mixing of the fluids occurs outside the mixing head. The connecting head also includes a channel to supply medicinal gas under pressure. The medicinal gas contacts the fluids at a mouth of the connecting head and conveys the fluids contained in the syringes to a surface.
Product literature commenting on a dual syringe device for delivering fibrinogen and thrombin and sold by the assignee of the ""055 patent, reports that the device operates at gas pressures of about 30-65 psi. If such devices are not properly used, the momentum of the pressurized gas, especially when conveying entrained fluids, could cause damage to tissue being treated by this device.
Two known devices in the prior art are disclosed in U.S. Pat. Nos. 5,368,563 to Lonneman et al. and 5,582,596 to Fukunaga et al. The ""563 patent discloses a large sprayer assembly in FIGS. 1-9 having a lateral feed conduit connecting two syringe connections to two mechanical breakup units. The syringes may contain separately a solution of fibrinogen and a solution of thrombin which are mixed to produce fibrin. The ""563 patent does not concern itself, however, with the possibility of unreacted fibrinogen. Further, due to the lateral feed requirements of the disclosed device, laparoscopic use of the preferred embodiment of the sprayer assembly device shown in FIGS. 1-9 is not possible. In fact, FIG. 10 teaches an alternate embodiment, showing the invention in conjunction with, for example, a catheter for possible laparoscopic procedures. In the alternate embodiment the spray assembly using the MBU is replaced with an intermediate plate 94 having multiple fluid paths (96, 98, 100, and 102) and a sprayer plate 104 with exit ports 106 and 108. The exit ports 106 and 108 are disclosed as analogous to the ports 72 and 74 of the MBU sprayer assembly (FIG. 9). However, the disclosed laparoscopic embodiment lacks the spin chamber, sloped walls, and other dimensional requirements provided by the present invention to achieve the proper circumjacent spray pattern of the two fluids, thereby substantially eliminating the occurrence of unreacted fibrinogen.
Likewise, the ""596 patent relates to a dual fluid applicator assembly. While the invention disclosed is directed to proper mixing of a fibrinogen solution with a thrombin solution on a surface, it attempts to achieve this goal using a sterile gas. The ""596 patent does not achieve a circumjacent spray of the two solutions, and does not make use of the unique properties provided by the MBU structure of the present invention.
Finally, a device sold by Johnson and Johnson provides for the application of a bovine thrombin and calcium chloride solution to a wound. In addition to possible issues raised by the use of bovine proteins, this procedure does not provide a satisfactory hemostasis function in high blood flow situations. The thrombin is believed to be washed from the wound site by the flow of blood.
The present invention, as set forth in the appended claims, overcomes these and other problems in prior art devices.
The present invention provides a medical device for delivering volumetric quantities of a first and a second biochemically reactive fluid. An embodiment or device comprises a first container having an opening and adapted to contain the first biochemically reactive fluid. A second container of this embodiment has a second fluid opening adjacent the first fluid opening and is adapted to contain the second biochemically reactive fluid. A spray unit is preferably in fluid communication with the first container and the second container, the spray unit being capable of separately atomizing the first and second biochemically reactive fluids into an aerosol with at least one energy source of either a liquid energy, a mechanical energy, a vibration energy, or an electric energy. A fluid pressurizer is preferably associated with the first and second containers for pressurizing the first and the second containers for delivery of the biochemically reactive fluids under pressure through the spray unit onto a surface. Wherein the first and second biochemically reactive fluids initially mix outside the delivery device (both in the air and on the surface).
The invention of the present application may be used to deliver biologicals such as collagen, photoactivable collagen, thrombin, photoactivable thrombin, tPA, photoactivable tPA, plasmin, photoactivable plasmin, urokinase, photoactivable urokinase, Factors VII, IX, X and XI, photoactivable Factors VII, IX, X and XI, albumin, photoactivable albumin, growing factors, cells, and fibrin. The following discusses the invention solely in terms of fibrin delivery, but those skilled in the art would understand its broader applications using other biologicals as well.
The present invention also provides a method for delivering fibrin to a surface. One embodiment method comprises the steps of: providing a liquid solution of fibrinogen, a liquid solution of thrombin, and a spray unit in fluid communication with the fibrinogen and thrombin solutions. The method further comprises spraying the fibrinogen solution and the thrombin solution separately onto the surface and mixing for the first time the fibrinogen with the thrombin on the surface to make fibrin.
This invention also provides a method for delivering fibrin to a surface within a cavity of a body of an animal to prevent the formation of adhesions. One embodiment of the method comprises a liquid solution of fibrinogen, a liquid solution of thrombin, and a spray unit in fluid communication with the fibrinogen and thrombin solutions. This method further comprises spraying the fibrinogen solution and the thrombin solution separately onto the surface with the spray unit, mixing for the first time the fibrinogen with the thrombin on the surface to make a fibrin film capable of preventing the formation of adhesions.
Preferably the medical devices of this invention operate at pressures that are generated by a hand-held device. This allows the present device to provide a cost effective and less complicated alternative to those medical devices that rely on pressurized gasses as a means for atomizing fluids and conveying them to a surface to be treated.
It is contemplated that versions of the medical device may be used in open-type surgeries such as laparotomic surgeries, topically and in minimally invasive surgeries such as laparoscopic surgeries. In open-type surgeries and minimally invasive surgeries, the present device may be used to achieve hemostasis, promote wound healing and for anti-adhesion purposes. In topical applications, the device may be used for treating burn patients during skin grafting procedures by delivering fibrin glue acting as a drug delivery vehicle for antimicrobial agent.
Specifically, with respect to laparoscopic surgeries, the present invention provides an embodiment of the delivery device using a spray assembly capable of delivering two reactive fluids through, for example, a catheter to be properly applied within the body cavity without the remnant of unreacted fluids. The delivery of one reactive fluid in a circumjacent cone with the other reactive fluid effects the desired mixing.
The disclosed medical devices are capable of simultaneously or sequentially delivering biochemically reactive fluids to a surface where they mix for the first time. In the sequential application, it is possible to repeat the procedure to incrementally form a fibrin film.